Apelin is an endogenous ligand for the angiotensin-1-like receptor APJ. Apelin is derived from a 77 amino acid precursor and processed into several active molecular forms including apelin-12, apelin-13, apelin-17 and apelin-36. Apelin is expressed in various organs, e.g. heart, lung, kidney, liver and other tissues. Apelin and the apelin receptor (APJ) are a G-protein coupled receptor system that has been found to be involved in pathological conditions involving angiogenesis, including cancer. Recently, apelin has been reported to be involved in hypoxia-induced retinal angiogenesis (Kasai et al. Arterioscler Thromb Vasc Biol 2010: 30, 2182-2187). It has also been reported that certain compositions may inhibit angiogenesis by inhibiting the apelin/APJ pathway (U.S. Pat. No. 7,736,646).
Apelin knockout mice have been shown to have impaired retinal vascularization and ocular development (Kasai et al. Arterioscler Thromb Vasc Biol 2008: 28, 1717-1722). The impaired vascular development occurred at least in the early postnatal period. Furthermore, it was suggested that apelin/APJ signaling was involved in a cooperative manner with VEGF or FGF2 in this condition.
It has also been reported that vitreous concentrations of apelin were significantly higher in patients having proliferative diabetic retinopathy (Tao et al., Invest Opthamol Visual Science 2010: 51, 4237-4242).